Preimplantation genetic diagnosis – Examining the embryo created by way of in vitro fertilisation

Preimplantation genetic diagnosis (PGD) gives hope to couples of giving birth to a healthy child – even if genetic predispositions are known or severe damage to the child’s health is probable.
Having been issued this licence, we are able to examine embryos created by way of artificial insemination by means of PGD, as one of the first reproductive centres in Germany. Our experienced physicians advise and accompany you during this process.

What exactly is PGD?

Preimplantation genetic diagnosis (PGD) is the genetic diagnosis of embryos having been created by way of in vitro fertilisation (IVF). These examinations include the in-depth screening for genetic abnormalities and chromosomal disorders, and shall be performed before the embryo is being transferred into the woman’s uterus, thus, before the start of a potential pregnancy. Consequently, PGD can exclusively be performed within artificial insemination, as it is the sole way to only abstract the relevant cells for analysis. In Germany, PGD can only be performed under certain conditions and with consent of an Ethics committee.

How PGD might help you.

PGD is helping couples who live at high risk of suffering from a severe hereditary disease due to their genetic constitution. The embryo is being examined for this genetic modification and will only be transferred into the uterus if there is no possible risk of disease.
PGD is only permitted to prevent miscarriage or stillbirth.

Benefits of treatment with us.

The MVZ PAN Institute of Endocrinology and Reproductive Medicine is one of the leading fertility clinics in Germany with more than 40 years of experience in the field of in vitro fertilisation. We have top quality standards and are certified by the German Technical Inspection Association (TÜV) as well as accredited by the official German Accreditation Body (DAkkS). Outstanding physicians and an experienced team are working together in the heart of Cologne to advise and care for you – before, during and after your PGD. You also benefit from our close collaboration with the Medical Genetics Centre in Munich (MGZ), the most prominent institution for genetic diagnosis throughout Germany.
Costs for putting in an application for the Ethics committee in Bavaria are about 180 to 300€.

The PGD process step by step.

For further details of the specific process, just click on the headline of each step.

(1) The couple’s inquiry at the MVZ PAN Institute

If you are interested in a medical consultation or just require more information, contact us by telephone (+49 221 2776 200) or email (repro@pan-klinik.de). Our team will get back to you as soon as possible to answer all your questions.

(2) Human genetic counselling at the MVZ PAN Institute

Our treatment will be based on your familial or genetic predispositions and diseases in order to ensure the best PGD examination possibilities. Our counselling includes an in-depth look into your family’s medical history by creating a family tree that extends over three generations.
Additionally, we will discuss possible prenatal screening methods and which of those are appropriate for your individual family situation. Depending on existing medical reports, we consider to do or rather repeat genetic examinations in the laboratory, which also performs the PGD.

(3) Reproductive medical counselling at the MVZ PAN Institute

We discuss the individual preconditions for a PGD in a consultation with our doctors, including examinations of the functional ovarian reserve (vaginal ultrasound, antral follicle count (AFC), Anti-Müllerian hormone (AMH)) as well as a semen analysis.

(4) Psychosocial counselling

The medical, psychological and social consequences of a PGD have to be discussed in detail prior to the consent to a PGD. This psychosocial counselling should be conducted by a doctor who is not involved in the procedure of the PGD.

The advisory statement by the MGZ in Munich and the human genetic report is required for the application for the Ethics committee, which presupposes that all consultations and examinations have taken place and that all open questions have been resolved.
It is legally required that the woman (whose oocytes are taken) has to make the application for a PGD at the interdisciplinary Ethics committee. Their judgement whether the PGD is within the law and thus, may be performed, is based on genetical, psychological, social and ethical factors. Both, our human geneticists and our Munich colleagues will gladly assist you with your application.
Our cooperation partner is the Bavarian Ethics Committee for Preimplantation Genetic Diagnosis. The group of experts is composed of 4 physicians (of the disciplines reproductive medicine, human genetics, paediatrics, psychiatry/psychotherapy), one lawyer, one ethicist, one patient representative and one representative from a support group for people coping with disabilities.

(6) IVF/ICSI treatment including biopsy on the embryos at the MVZ PAN Institute

Having received a positive feedback from the committee, the treatment may begin. To examine the embryos, they have to be produced outside the woman’s body. The process involves ovarian stimulation, removing an ovum from the ovaries and injecting a single sperm (regardless of the findings of the semen analysis) directly into an egg (ICSI) to avoid absorbing damaged strands of DNA when taking the biopsy on the embryo later. The fertilised eggs evolve into embryos, which are incubated in the embryoscope for further growing. On the third day, a laser perforates the outer shell (zona pullucida) of the embryo in a single spot, which is used for the biopsy as soon as the embryo developed into the blastocyst. Each embryo will be fixed under the microscope to extract about eight cells with a high precision laser for further analysis. The samples are sent to the MGZ in Munich for genetic analysis, while the embryos are cryopreserved by vitrification and stored until further utilisation.

(7) Genetic examination of embryotic cells at the MGZ in Munich

Before performing a PGD, it is necessary to clarify whether a definite detection of the known mutation(s) in your and/or your partner’s body is even possible, no matter whether examining just one or more cells. This usually requires another blood sampling, which is sent to the MGZ in Munich and tested for prescribed mutation(s) and chromosomal alterations. This is usually only done once before your first PGD. Rarely, it is impossible (for methodical and technical reasons) to perform PGD after the establishment of a diagnosis.

(8) Transfer of suitable embryos at the MVZ PAN Institute

The results of the genetic diagnostics are communicated from the MGZ in Munich to our doctors at the MVZ PAN Institute. At this point it is known, which embryos are suffering from the genetic disease and thus, which embryo is suitable for transfer into the uterus.
It is possible that the results indicate that none of the embryos are suitable for transfer.
For the transfer, the embryo is thawed and, after a small hormonal pre-treatment, is being transferred into the uterus with a thin catheter. This minor intervention does not require anaesthesia. After resting for a short period of time, you can go home the same day.

Do you have any questions or want to make an appointment?
Do not hesitate to ask!

Who performs the PGD?

The MVZ PAN Institute in Cologne performs the PGD in close collaboration with the Medical Genetics Centre in Munich (MGZ). This cooperation was recently certified by the Bavarian State Ministry of Health and Care.
The MVZ PAN Institute is responsible for the human genetic and reproductive medical counselling as well as the IVF/ICSI treatment including the biopsy on the embryos. The PGD, meaning the genetic analysis of cells, is done at the MGZ in Munich. The final results are sent to Cologne, where the doctors discuss them with the couple and, if there is a suitable one, the embryo is being transferred into the woman’s uterus.

Costs of a PGD.

The costs for the individual analysis may vary immensely; some known chromosomal alterations require different laboratory steps than the analysis of monogenic diseases. If you are suffering from chromosomal alterations, costs per cycle for the establishment and examination of the embryo amount to 1,200€, for any further embryo examined (in this cycle) costs amount to an additional 530€ (status as of August 2017). A molecular genetic analysis requires first of all the establishment of your family specific alterations. This is usually only done once before your (potential) PGD, which is why the costs of about 3,100€ (status as of August 2017) only arise once. Every PGD-cycle additionally costs about 2,100€ (status as of August 2017). Additional costs incur for the human genetic counselling within the context of the PGD.
Usually, health insurances do not absorb these costs and a cost absorption must be requested and is examined individually.

Collection of polar bodies vs. biopsy on trophoblasts.

To collect genetic material from the pre-embryo for a PGD in the course of in vitro fertilisation (IVF/ICSI), it is possible to collect polar bodies or take a biopsy on trophoblasts during the embryonic blastocyst stage.

Both polar bodies are formed when the oocytes mature and geminate after the sperm penetrates the ovum and the following formation of pronuclei (pronuclear/PN stage). To draw conclusions with regard to the complete set of chromosomes as well as the ovum’s mutation status, both polar bodies must be examined. The complete collection of both polar bodies is, however, at times difficult due to the possibility of (at least) one fragmented polar body. When performing a biopsy on trophoblasts though, about 6-8 cells can be collected, which allows a more accurate prediction.

After collecting both polar bodies, the nascent embryos are further cultivated up to the blastocyst-stage. The evolved blastocysts are cryopreserved (vitrification) until the human genetic results are available, similar to the trophoblast-biopsy. The human genetic diagnostics is usually made with molecular genetic techniques (Next Generation Sequencing/NGS, etc.).

The biopsy on trophoblasts requires a positive feedback from the competent ethics committee (PGD), while a polar body biopsy does not necessitate consent. However, a polar body biopsy may only detect inherited diseases and predispositions within the mother’s genetic code, while the biopsy on trophoblasts includes the father’s genetic code, too.

Dr Stefan Palm, MD

Specialist for Gynaecology, Gynaecological Endocrinology and Reproductive Medicine, Medical Director of the MVZ PAN Institute and the PAN Clinics.palm@pan-klinik.de